We propose to study the nutritional and metabolic capacity of the neonatal rat over the period when milk is the primary dietary source. An artificial rearing system for rats 5 to 23 days of age will be introduced to facilitate the study. Initially the metabolism of glucose, lactate, acetoacetate and D(-)-3-hydroxybutyrate will be investigated during this period of development. The production and utilization of these four primary carbon sources for respiration and lipid synthesis will be studied in relation to (1) the enhanced and reduced availability of acetoacetate and D(-)-3-hydroxybutyrate (ketone bodies) on the metabolism of glucose and lactate and on the metabolic welfare of the neonate (2) the enhanced and reduced availability of glucose and/or lactate on the metabolism of the ketone bodies and the capacity of the neonate to metabolize lactate. The experiments are designed to establish the relative importance of the ketone bodies and glucose for respiration and lipid synthesis during development. It is proposed that lactate produced by active glycolysis in brain and certain peripheral tissues is utilized by active gluconeogenesis in liver and kidney for the maintenance of glucose homeostasis. We propose that a rapid glucose-lactate cycle exists under normal physiological and resting conditions during development. The effect of various ketone body levels on glucose-lactate metabolism and on pyruvate metabolism to acetyl-CoA will be studied. The pattern of development of pyruvate dehydrogenase in organs of the neonate during development will be determined in relation to the metabolic status of the animal. We plan to find out if the normal pattern of induction of pyruvate dehydrogenase can be suppressed or delayed depending on the metabolic status of the ketone bodies. Metabolic and enzymic conditions which could simulate an energy deficit will be probed. The concentration of acetoacetate D(-)-3-hydroxybutyrate, glucose and lactate in blood, the rates of their utilization from blood, the flux of carbon from each of these metabolites into sterols and fatty acids in organs and the status of the glucose-lactate cycle as measured with specific 14C labeled glucose and lactate are criteria which will be used to study the nutritional and metabolic capacity of the neonate during development.